IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

four days). In hepatic tissue, 1.16 ± 0.2 adducts per 10 8 nucleotides were detected;
slightly higher adduct levels were found in kidneys and duodenum, namely 2.19 ± 1.2
and 1.91 ± 0.6, respectively (Poginsky et al., 1991). The only genotoxicity assay in
which lucidin gave a negative response was the Drosophila wing-spot test.
4.5 Mechanistic considerations
1-Hydroxyanthraquinone
SOME TRADITIONAL HERBAL MEDICINES 145
There is some evidence that 1-hydroxyanthraquinone is genotoxic. In rats, induction
of cell proliferation in vivo was seen in the caecum which was paralleled by enhanced
ornithine decarboxylase activity (Mori et al., 1992). In a combination experiment with
methylazoxymethanol acetate (given by single intraperitoneal injection) and 1-hydroxyanthraquinone
(1% in diet; 40 weeks), the level of tumour necrosis factor α was
increased when rats were exposed to the combination compared with the groups that
received either compound alone. It was postulated that this might account for the synergistic
carcinogenic effect of these compounds (see Section 3.2.2) (Yoshimi et al., 1994).
In studies of mutations in cancer-related genes from tumours of rats exposed to methylazoxymethanol
acetate and 1-hydroxyanthraquinone, specific mutations were found in
the gene encoding β-catenin but not in other genes such as apc (Suzui et al., 1999).
1,3-Dihydroxy-2-hydroxymethylanthraquinone (lucidin)
Lucidin is genotoxic in vitro and in vivo (Westendorf et al., 1988). Data on carcinogenic
activity of this compound were not available, but it has been shown that madder
root (Rubia tinctorum) — which contains lucidin — causes tumours in liver and kidneys
of rats. The DNA-adduct pattern from colon, liver and kidneys of rats showed one adduct
that was also found when deoxyguanosine-3′-monophosphate was incubated with lucidin
in vitro. This supports the assumption that lucidin is involved in the carcinogenic
effects of Rubia tinctorum (Westendorf et al., 1998). It has been hypothesized that lucidin
is activated by phase II enzymes through substitution of the hydroxymethyl group,
followed by hydrolytic cleavage, leading to the formation of a DNA-reactive methylene
metabolite or carbenium ion (Poginsky et al., 1991).